Cardiac α-myosin heavy chains differ in their induction of myocarditis: Identification of pathogenic epitopes

Li Liao, Rajeev Sindhwani, Leslie Leinwand, Betty Diamond, Stephen Factor

Research output: Contribution to journalArticlepeer-review

48 Scopus citations

Abstract

BALB/c mice develop autoimmune myocarditis after immunization with mouse cardiac myosin, whereas C57B/6 mice do not. To define the immunogenicity and pathogenicity of cardiac myosin in BALB/c mice, we immunized mice with different forms of cardiac myosin. These studies demonstrate the discordance of immunogenicity and pathogenicity of myosin heavy chains. The cardiac α-myosin heavy chains of BALB/c and C57B/6 mice differ by two residues that are near the junction of the head and rod in the S2 fragment of myosin. Myosin preparations from both strains are immunogenic in susceptible BALB/c as well as in nonsusceptible C57B/6 mice; however, BALB/c myosin induces a greater incidence of disease. To further delineate epitopes of myosin heavy chain responsible for immunogenicity and disease, mice were immunized with fragments of genetically engineered rat α cardiac myosin. Epitopes in the region of difference between BALB/c and C57B/6 (residues 735-1032) induce disease in both susceptible and nonsusceptible mice. The data presented here demonstrate that pathogenic epitopes of both mouse and rat myosin reside in the polymorphic region of the S2 subunit. In addition, these studies suggest that polymorphisms in the autoantigen may be part of the genetic basis for autoimmune myocarditis.

Original languageEnglish
Pages (from-to)2877-2882
Number of pages6
JournalJournal of Clinical Investigation
Volume92
Issue number6
StatePublished - Dec 1993
Externally publishedYes

Keywords

  • Autoimmunity
  • Cardiology
  • Lymphocytes
  • Myocarditis
  • Myocardium

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